Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10–5.17, P-value = 0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63–3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI=1.10-5.17, P-value=0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI=0•63-3•16, P-value=0•395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies. Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768)

Introduction The effectiveness of umifenovir against COVID-19 is controversial; therefore, clinical trials are crucial to evaluate its efficacy. Methods The study was conducted as a single-center, randomized, open-label clinical trial. Eligible moderate-severe hospitalized patients with confirmed SARS-Cov-2 infection were randomly segregated into intervention and control groups. The intervention group were treated with lopinavir/ritonavir (400 mg/100 mg bid for 10–14 days) + hydroxychloroquine (400 mg single dose) + interferon-β1a (Subcutaneous injections of 44 µg (12,000 IU) on days 1, 3, 5) + umifenovir (200 mg trice daily for 10 days), and the control group received lopinavir/ritonavir (same dose) + hydroxychloroquine (same dose) + interferon-β1a (same dose). Results Of 1180 patients with positive RT-PCRs and positive chest CT scans, 101 patients were finally included in the trial; 50 were assigned to receive IFNβ1a + hydroxychloroquine + lopinavir/ritonavir group and 51 were managed to treat with IFNβ1a + hydroxychloroquine + lopinavir/ritonavir + umifenovir. Since all patients received the intended treatment as scheduled, the analysis just included as the ITT population. Time to clinical improvement (TTCI) did not hold a statistically significant difference between intervention and control groups (median, 9 days for intervention group versus 7 days for the control group; P: 0.22). Besides, Hazard Ratio for TTCI in the Cox regression model was 0.75 (95% CI: 0.45–1.23, P:0.25) which also confirmed that there was no statistically significant difference between the treatment group and the control group. The mortality was not statistically significant between the two groups (38% in controls vs 33.3% treatment group). Conclusions Our findings shed new lights on the facts that additional umifenovir has not been found to be effective in shortening the duration of SARS-CoV-2 in severe patients and improving the prognosis in non-ICU patients and mortality. Trial registration The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04350684.

Introduction Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high-dose IFN-β 1a compared to low dose IFN-β 1a in severe COVID-19 cases. Methods In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high-dose IFN-β 1a (Recigen) (Subcutaneous injections of 88μg (24 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally) and the control group was treated with low-dose IFN-β 1a (Recigen) (Subcutaneous injections of 44μg (12 million IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally). Result A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low-dose IFN-β1a was shorter than that for cases treated with high-dose IFN-β1a (6 vs 10 days; P=0.018). The mortality rates in intervention and control group were 41% and 36.5%, respectively. Conclusion The use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it did not have any significant effect on mortality reduction compared with treating with low-dose IFN-β 1a. Trial registration: This trial has been registered as ClinicalTrials.gov, NCT04521400.

Background: The scientific evidence concerning pathogenesis and immunopathology of the coronavirus disease 2019 (COVID-19) is rapidly evolving in the literature. To evaluate the different tissues obtained by biopsy and autopsy from five patients who expired from severe COVID-19 in our medical center. Methods: This retrospective study reviewed five patients with severe COVID-19, confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and imaging, to determine the potential correlations between histologic findings with patient outcome. Results: Diffuse alveolar damage (DAD) and micro-thrombosis were the most common histologic finding in the lung tissues (4 of 5 cases), and immunohistochemical (IHC) findings (3 of 4 cases) suggested perivascular aggregation and diffuse infiltration of alveolar walls by CD4+ and CD8+ T lymphocytes. Two of five cases had mild predominantly perivascular lymphocytic infiltration, single cell myocardial necrosis and variable interstitial edema in myocardial samples. Hypertrophic cardiac myocytes, representing hypertensive cardiomyopathy was seen in one patient and CD4+ and CD8+ T lymphocytes were detected on IHC in two cases. In renal samples, acute tubular necrosis was observed in 3 of 5 cases, while chronic tubulointerstitial nephritis, crescent formation and small vessel fibrin thrombi were observed in 1 of 5 samples. Sinusoidal dilation, mild to moderate chronic portal inflammation and mild mixed macro- and micro-vesicular steatosis were detected in all liver samples. Conclusion: Our observations suggest that clinical pathology findings on autopsy tissue samples could shed more light on the pathogenesis, and consequently the management, of patients with severe COVID-19.

<b><i>Introduction:</i></b> Uncontrolled overproduction of inflammatory mediators is predominantly observed in patients with severe COVID-19. The excessive immune response gives rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients. <b><i>Method:</i></b> We conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and continuous renal replacement therapies were initiated in the hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, oxygen saturation (SPO2) at the admission, and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron^© (HA330) and CytoSorb® 300. <b><i>Result:</i></b> A total of 128 COVID-19-confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission day in the control and hemoperfusion groups was 80% and 75%, respectively (<i>p</i> value = 0.113). The mortality rate was significantly lower in the hemoperfusion group compared to the matched group (67.3% vs. 89%; <i>p</i> value = 0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; <i>p</i> &#x3c; 0.001). The median final SPO2 was statistically higher in the hemoperfusion group than in the matched group, and the median PaCO2 was lower. <b><i>Conclusion:</i></b> Among critically ill COVID-19 patients, based on our study, the use of hemoperfusion may reduce the mortality rate and improve SPO2 and PaCO2.

IntroductionIn critically ill COVID-19 patients, uncontrolled over-production of inflammatory mediators is observed, dominantly. The excessive immune response give rise to multiple organ dysfunction. Implementing extracorporeal therapies may be useful in omitting inflammatory mediators and supporting different organ systems. We aimed to investigate the effectiveness of hemoperfusion in combination with standard therapy in critically ill COVID-19 patients.MethodWe conducted a single-center, matched control retrospective study on patients with confirmed SARS-CoV-2 infection. Patients were treated with hemoperfusion in combination with standard therapy (hemoperfusion group) or standard treatment (matched group). Hemoperfusion or hemoperfusion and CRRT (continuous renal replacement therapy) therapies were initiated in hemoperfusion group. The patients in the matched group were matched one by one with the hemoperfusion group for age, sex, the oxygen saturation (SPO2) at the admission and the frequency of using invasive mechanical ventilation during hospitalization. Two types of hemoperfusion cartridges used in this study were Jafron© (HA330) or cytosorb® 300. ResultA total number of 128 COVID- 19 confirmed patients were enrolled in this study; 73 patients were allotted to the matched group and 55 patients received hemoperfusion. The median SPO2 at the admission in control and hemoperfusion groups was 80% and 75%, respectively (P-value=0.113). The mortality rate was significantly lower in hemoperfusion group compared to the matched group (67.3% vs. 89%; P.value=0.002). The median length of ICU stay was statistically different in studied groups (median, 12 days for hemoperfusion group vs. 8 days for the matched group; P<0.001). The median of final oxygen saturation was statistically higher and median of PaCO2 was lower in hemoperfusion group compared to the matched group.ConclusionAmong critically ill COVID-19 patients, the use of hemoperfusion reduces the mortality rate and improves oxygen saturation and PaCO2.

Background: Platelet volume indices (PVIs) are inexpensive and readily available parameters in intensive care units (ICUs). However, their association with mortality has never been investigated in the post-neurosurgical meningitis (PNM). Objectives: This study was designed to investigate the association of PVIs with mortality in PNM patients. Methods: This retrospective study was conducted in the adult patients undergone various neurosurgical procedures in a neurosurgery department at a tertiary educational medical center in Tehran from 2016 to 2017. In this study, platelet indices including mean platelet volume (MPV), platelet distribution width (PDW), and platelet count were measured on ICU admission. Results: A total of 37 patients were included, 18 of whom survived (mortality rate: 50%). PDW and MPV values were significantly higher in non-survivors than in survivors. In non-survivor patients, platelet count was significantly lower and PDW was higher at diagnosis and discharge when compared to on admission. Also, there was no significant linear correlation between Charlson comorbidity index (CCI) and platelet indices. The means of these parameters showed no significant differences in CCI categories between the two patient subgroups. Conclusions: The obtained data revealed that the high levels of MPV and PDW in PNM are not associated with the increased risk of mortality, whereas the decrease in plateletcrit was not associated with increased risk of mortality.